This career development proposal aims to provide the necessary protected research time and training for Dr. Demmer to transition from his postdoctoral research position to an independent tenure track faculty position. The proposal is comprised of two phases: 1) A mentored phase focused on strengthening the candidate's publication record and obtaining additional training in research areas outside of the candidate's current expertise; and 2) a comprehensive research project to be carried out upon procurement of a research track faculty position. The proposed training will be carried out in the Mailman School of Public Health at Columbia University Medical Center. Specifically, the mentored postdoctoral phase will provide opportunities for advanced training in the following four modules: Module 1) Advanced measurement methods with focus on methodological approaches to quantifying infection as an etiologic exposure for chronic disease; Module 2) Type 2 diabetes mellitus epidemiology and pathophysiology; Module 3) Genomics, with an emphasis in bioinformatics and gene expression studies; Module 4) Dissemination of scientific findings and grant writing. The independent phase research aims to test the hypothesis that periodontal infection is an etiologic factor in the development of type 2 diabetes mellitus (DM). Dr. Demmer proposes to study whether baseline exposure to known periodontal pathogens is associated with progression of DM risk factors over two years of longitudinal follow-up. Dr. Demmer and colleagues will assess the two year progression of fasting glucose, insulin resistance and beta-cell dysfunction and compare these progression rates between participants with high vs. low colonization levels of selected periodontal pathogens. This will be achieved using a longitudinal cohort design among n=300 participants in a population of tri-ethnic men and women aged 30 - 55 years at baseline enrollment. The proposed design will carefully control for potential confounders such as baseline levels of fasting glucose, insulin, lipids, obesity, diet, age, smoking, ethnicity and gender. The proposed research can advance the scientific knowledge regarding the well-known association between periodontal infection and type 2 diabetes mellitus through its provision of a powerful study design appropriate for addressing temporality (i.e., do periodontal infections precede the onset of diabetes pathology). In addition, data on the independent contribution of infections to the underlying pathology of diabetes can be addressed for the first time using a population based, chronic infection model. The independent phase research project will significantly enhance the applicant's qualifications to serve as principal investigator on a future R-01 application - an explicit aim of this funding mechanism. [unreadable] [unreadable] [unreadable]